Pemphigus herpetiformis: from first description until now.

Pemphigus herpetiformis is one of the less common forms of pemphigus, first introduced by Jablonska and colleagues in 1975. This autoimmune bullous disease combines the clinical features of dermatitis herpetiformis and the immunologic characteristics of pemphigus. The target autoantigen is usually desmoglein 1 (or less frequently desmoglein 3), although recently it has become increasingly obvious that patients with pemphigus herpetiformis also demonstrate autoantibodies against desmocollin. Here, we summarize reported cases of pemphigus herpetiformis and describe current knowledge considering epidemiology, clinical manifestations, histologic findings, immunopathology, pathophysiologic concepts, associated diseases, and treatment of this rare disorder.

Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical presentation.

Dermatitis herpetiformis (DH) is an autoimmune disease that is linked to gluten sensitivity and has a clear relationship to celiac disease. Both conditions are mediated by the IgA class of autoantibodies and the diagnosis of DH is dependent on detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH but environmental factors are also important. Typically, young adults present with excoriations only, as the severe pruritus effectively destroys any primary lesions. Based upon our experience with DH and a comprehensive literature review, we provide an update of DH epidemiology, pathophysiology, and clinical presentation.

[Dermatitis herpetiformis: a review]. / Dermatite herpétiforme: revue de la littérature.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare auto-immune bullous disease characterized by its almost constant association to gluten sensitivity. OBJECTIVE: Review of literature about epidemiology, physiopathology, clinical data and treatment of DH. METHODS: Research on Medline and Embase database without any time limit until April 2010. Because of the lack of randomized therapeutic trials in DH, retrospective series and case reports have been analyzed. RESULTS: DH is related to auto-antibodies against epidermal transglutaminase, which belongs to the same family as tissue transglutaminase, the auto-antigen of celiac disease. Physiopathology is complex, occurring in HLA DQ2 or DQ8 predisposed patients, and implies gluten, immunological reaction in the intestinal wall then in the skin. DH and celiac disease may be encountered in the same family. DH is characterized by a very pruritic microvesicular eruption typically located on elbows, knees and buttocks. Digestive manifestations of celiac disease occur in 15% of cases. Direct immunofluorescence is necessary to confirm the diagnosis, showing granular IgA±C3 deposits in the papillary dermis. Circulating IgA and IgG antiendomysium and antitransglutaminase antibodies are detected in almost all patients at the acute phase and follow the clinical course of the disease. Gastro-intestinal endoscopy with multiple duodenal biopsies shows partial or complete villous atrophy in two thirds of cases, intraepithelial lymphocyte infiltrate in the other cases. Other auto-immune diseases may be associated in 10-20% of cases. The main long-term risk is the occurrence of T or B nodal or intestinal tract lymphoma in 2% of cases (relative risk close to 6 in several studies, but not admitted by all authors), especially if adherence to gluten-free diet is not strict. Treatment is based on dapsone, which is quickly efficient on cutaneous manifestations, but not on the digestive involvement and on strict and definitive gluten-free diet, which cures villous atrophy and reduces the risk of lymphoma. CONCLUSION: DH is associated to a gluten enteropathy and its physiopathology is better known. Even if the risk of secondary lymphoma seems little, most of the authors recommend a definitive gluten-free diet.

Remission in dermatitis herpetiformis: a cohort study.

OBJECTIVES: To determine the percentage of patients with dermatitis herpetiformis (DH) who experience at least 2 years of remission and to identify factors associated with DH remission. DESIGN: Retrospective cohort study. SETTING: National Institutes of Health (NIH). PATIENTS: Patients seen at the NIH during the 1972-2010 period who had clinical findings consistent with DH, whose normal skin showed the presence of granular IgA deposits at the dermoepidermal junction on direct immunofluorescence (DIF) examination, whose age of disease onset was known, who had DH for at least 2 years, and who were followed up for at least 3 years after the initial NIH visit. MAIN OUTCOME MEASURE: Remission, defined as absence of skin lesions and symptoms of DH for more than 2 years while not taking sulfones (dapsone or sulfoxone), sulfapyridine, anti-tumor necrosis factor agents, or oral steroids and not adhering to a gluten-free diet. RESULTS: Among 86 patients, in 10 (12%) the disease underwent remission (95% confidence interval, 6%-20%). Factors associated with DH remission included DH age of onset at 39 years or older vs onset at ages 8 to 38 years (unadjusted P = .02; adjusted P = .07) and DH onset year between 1960 and 1972 vs onset between 1935 and 1959 or after 1972 (P = .02 for global comparison of 4 onset-year groups). CONCLUSIONS: Dermatitis herpetiformis can go into remission. Clinicians should attempt to wean patients with well-controlled DH from a gluten-free diet and/or use of sulfones or other therapies to determine if the DH might have remitted. Our findings provide insight into the pathogenesis and course of this disease and may serve to guide long-term management of patients with DH.

What lies beneath the surface of the itch in adults?

Pruritus is synonymous with itching. Many medical conditions are complicated by chronic pruritus compromising the patient's quality of life. The majority of pruritic stimuli are transmitted through C fibers into the lateral spinothalamic tract and then into the somatic sensory cortex where the itching is detected. Histamine, substance P, and tumor necrosis factor a play significant roles in the perception of pruritus. Medical conditions in adults with significant pruritus will be defined in this review.

Oral and vulvar changes in pregnancy.

The endocrinologic, immunological, and vascular changes that occur during pregnancy are far-reaching. These systemic factors produce profound local impact on the physiology and pathology of the oral cavity, vagina, and vulva. Physiological changes can be expected and tolerable or of such severity that they are viewed as pathological. Existing disease can be exacerbated and dermatoses specific to pregnancy can erupt. Each of these conditions can pose potentially challenging treatment considerations.

Dermatite herpetiforme: manifestações cutâneas e bucais / Dermatitis herpetiformis: cutaneous and oral manifestations

Os autores realizaram uma revisão da literatura sobre dermatite herpetiforme (DH), apresentando os acometimentos cutâneos e bucais. Tal enfermidade, de provável etiologia auto-imune, consiste de uma doença crônica vesicobolhosa caracterizada clinicamente por pápulas e vesículas pruriginosas. Microscopicamente, através de fluorescência, pode ser observada a presença de depósito granular de IgA ao longo de membrana basal. Há associação entre pacientes portadores de DH e a sensibilidade ao glúten, esse achado também encontrado na doença celíaca. O tratamento recomendado para essa enfermidade é medicamentoso associado a uma dieta livre de glúten. Neste artigo discorre-se sobre etiologia, relações com enteropatia, influência do glúten, tratamento e diagnósticos diferenciais.

Bone mass and metabolism in dermatitis herpetiformis.

Dermatitis herpetiformis is a gluten-sensitive skin disease with intestinal lesions and malabsorption symptoms less severe than those found in celiac disease. While several studies have shown the occurrence of osteopenia in celiac disease, bone mass and metabolism have never before been evaluated in dermatitis herpetiformis. Therefore, in 16 untreated patients, 16 sex- and age-matched untreated celiac patients, and 16 sex- and age-matched healthy volunteers, lumbar and femoral bone mineral density were measured and bone and mineral metabolism and nutritional status were evaluated. All these parameters were significantly altered in the two groups of patients and although the degree of these alterations was milder in patients with dermatitis herpetiformis than in celiac patients, the presence of subtotal villous atrophy in patients with dermatitis herpetiformis was associated with the presence of more severe alterations. Bone mineral density was significantly correlated with nutritional status, and patients showing bone loss were characterized by a body mass index lower than 20. Alterations of bone mass and mineral metabolism complicate dermatitis herpetiformis when severe intestinal lesions coexist. A low nutritional status may be predictive of the presence of bone loss.

Absence of toxicity of oats in patients with dermatitis herpetiformis.

BACKGROUND: People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS: We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS: None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS: Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

Dermatite herpetiforme / Dermatitis herpetiformis

A dermatite herpetiforme é uma doença bolhosa crônica, sensível ao glúten, relacionada a us risco aumentado para o desenvolvimento de linfoma. Através deste artigo, foi realizada uma revisão bibliográfica sobre seus aspectos epidemiológicos clínicos e terapêuticos.

Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease, that is associated with an increased risk for lymphoma. It was made a bibliographic review about its epidemiological, clinical and therapeutical features.

Dermatite herpetiforme como manifestacao paraneoplasica de carcinoma de colo de utero: apresentacao de um caso / Dermatitis herpetiformis as paraneoplastic manifestation of uterine cervix carcinoma: a case-report

A dermatite herpetiforme ou dermatite de Duhring-Brocq e uma dermatose bolhosa caracterizada por lesoes polimorficas compostas de papulas, vesiculas, bolhas e crostas intensamente pruriginosas. Histologicamente, uma bolha subepidermica e formada, principalmente com infiltrado neutrofilico, fibrina e edema. Essa dermatose pode ser uma manifestacao paraneoplasica de diversos tumores malignos, mas raramente relaciona-se a neoplasias de cervice uterina. Os autores apresentam um caso de dermatite herpetiforme como dermatose paraneoplasica de carcinoma de colo de utero

Small intestinal function and dietary status in dermatitis herpetiformis.

Small intestinal morphology and function were assessed in 82 patients with dermatitis herpetiformis, 51 of whom were taking a normal diet and 31 a gluten free diet. Methods used were histopathological evaluation of jejunal mucosal biopsy specimens, quantitation of intraepithelial lymphocytes, cellobiose/mannitol permeability test, tissue disaccharidase values, serum antigliadin antibodies, and formal assessment of dietary gluten content by a dietician. There was no correlation between dietary gluten intake and the degree of enteropathy in the 51 patients taking a normal diet, whereas biopsy specimens were normal in 24 of the 31 patients on a gluten free diet, all previously having been abnormal. Eighteen patients on gluten containing diets had normal jejunal histology and in seven of these all tests of small intestinal morphology and function were entirely normal. Intestinal permeability was abnormal and serum antigliadin antibodies were present in most patients with enteropathy. Studies of acid secretion in seven patients showed that hypochlorhydria or achlorhydria did not lead to abnormal permeability in the absence of enteropathy. This study shows that a combination of objective tests of small intestinal architecture and function will detect abnormalities in most dermatitis herpetiformis patients, including some with histologically normal jejunal biopsy specimens. Nevertheless there is a small group in whom all conventional intestinal investigations are entirely normal.

Cutaneous IgA deposits in bullous diseases function as ligands to mediate adherence of activated neutrophils.

Linear IgA bullous dermatosis and dermatitis herpetiformis are inflammatory subepidermal blistering diseases characterized by IgA deposits at the cutaneous epithelial basement membrane and in dermal papillae, respectively. Inflammation in both disorders localizes to sites of IgA deposition and is characterized by a predominance of neutrophils. From these observations we postulate that IgA deposits in both diseases may contribute to the recruitment and/or localization of neutrophils. In this study we examined the ability of in vitro and in vivo bound IgA anti-basement membrane autoantibodies from patients with linear IgA bullous dermatosis and in vivo bound IgA deposits in dermal papillae from patients with dermatitis herpetiformis to mediate adherence of neutrophils stimulated by granulocyte macrophage colony-stimulating factor. The study showed that stimulated neutrophils adhered to basement membranes and dermal papillae containing IgA deposits. Adherence was IgA anti-basement membrane antibody concentration dependent and correlated with the immunofluorescence staining intensity of IgA deposits in dermal papillae. Adherence to IgA deposits but not IgG deposits could be inhibited by purified exogenous secretory IgA but not IgG and adherence to IgG deposits could be inhibited by purified exogenous IgG but not secretory IgA. These results provide direct experimental evidence that cutaneous IgA deposits in linear IgA bullous dermatosis and dermatitis herpetiformis can function as ligands for neutrophil adherence and have a role in the localization of inflammation in these disorders.

Nutritional status in patients with dermatitis herpetiformis.

Nutritional status of 86 patients with dermatitis herpetiformis (DH) was defined by anthropometric measurements and hematological and biochemical laboratory tests to establish prevalence of malabsorption and malnutrition. Anthropometric measurements in DH patients were comparable to normal control patients. Four individuals were of short stature; two had had diarrhea and failed to thrive in childhood. Abnormalities attributable to nutritional deficiency were detected in only 6 of the 86, whereas drug-associated hematological or biochemical changes were present in 36 of 55 subjects treated with dapsone or sulfapyridine. Twenty patients had hemolytic anemia or macrocytosis related to drug therapy. Only two had anemias attributable to malabsorption; one was iron deficient, the other folate deficient. Two other patients were mildly Fe deficient and two had slight folate deficiency; they lacked other stigmata of malabsorption. Drug-induced hematological and biochemical abnormalities were more common than changes that suggest nutritional disease, even though most DH patients had an enteropathy at presentation.

Small intestinal permeability in dermatological disease.

Passive small intestinal permeability was investigated in 62 patients with atopic eczema, 29 with psoriasis and 18 with dermatitis herpetiformis, using the cellobiose/mannitol differential sugar absorption test. Urinary recovery of cellobiose and mannitol in patients with both psoriasis and eczema were similar to values in a control population, and were not affected by the extent or activity of skin disease. The cellobiose/mannitol recovery ratio was abnormally high in seven patients with eczema, six of whom underwent jejunal biopsy. Jejunal mucosal morphology was normal in five, and one patient was found to have coeliac disease. Cellobiose/mannitol recovery ratio was also abnormal in seven patients with psoriasis, and in 11 with dermatitis herpetiformis, seven of whom had a normal jejunal biopsy. These findings demonstrate that the passive permeability of the small intestine is normal in the majority of patients with atopic eczema and psoriasis. Increased absorption of macromolecules from the gut lumen cannot be ascribed to defective intestinal integrity, and is unlikely to be relevant to the pathogenesis of eczema. Abnormal intestinal permeability may be a more sensitive manifestation of gluten-sensitive enteropathy than jejunal biopsy in dermatitis herpetiformis.

Gastric morphology and function in dermatitis herpetiformis and in coeliac disease.

Gastric acid secretory capacity was evaluated in 116 patients with dermatitis herpetiformis by means of the pentagastrin test. Endoscopic gastric mucosal biopsy specimens were obtained from both the body and the antrum in 90 of them. Forty-eight patients (41%) had a maximal acid output less than 10 mmol/h, and 30 of them (26%) were achlorhydric. The frequency of achlorhydria increased with age, and 27 out of 58 patients (47%) more than 50 years old were achlorhydric. Antrum-sparing chronic atrophic gastritis was present in 92% of the achlorhydric patients, and hypergastrinaemia and serum parietal cell antibodies were found in most of them. The prevalence of chronic gastritis of the body and of the antrum increased with age. There was no correlation between atrophic gastritis or achlorhydria and small-intestinal villous atrophy, the results of the D-xylose test, and blood folate and serum zinc determinations. The transferrin saturation index was lower in patients with achlorhydria. The frequency of achlorhydria was significantly higher in patients with dermatitis herpetiformis than in 69 patients with coeliac disease.

Iron absorption in patients with dermatitis herpertiformis.

Iron absorption has been studied in patients with dermatitis herpetiformis (DH). Four patients out of 20 had iron deficiency, defined as absence of or only traces of haemosiderin in bone marrow smears. These four had adequate absorption of ferrous iron. The iron deficiency in at least 3 of them was ascribed to increased iron loss. The results indicate that, although having a mild to moderate malabsorption syndrome, DH patients can be expected to exhibit adequate absorption of orally administered iron. Explanations of a negative iron balance other than defective absorption should therefore be sought.